P1123: TEMPO: A PHASE 2, RANDOMIZED, OPEN-LABEL, 2-ARM STUDY COMPARING TWO INTERMITTENT DOSING SCHEDULES OF DUVELISIB IN SUBJECTS WITH INDOLENT NON-HODGKIN LYMPHOMA (INHL)
Authors: V. Vorobyev, D. H. Yoon, M. Kaźmierczak, S. Grosicki, C. Tarella, A. Genua, J. S. Kim, D. Cohan, M. Daugherty, I. W. Flinn, P. L. Zinzani, L. I. Gordon
Journal: HemaSphere (2022)

Background: Dosing of duvelisib at 25 mg orally BID has been shown to be active in iNHL, as the pivotal phase 2 DYNAMO study (NCT01882803) in iNHL met its primary endpoint of overall response rate (ORR) assessed by an IRC. Aims: The TEMPO study (NCT04038359; supported by Secura Bio) examined the effects of prespecified 2-week dose holidays on tumor responses and safety/tolerability in patients (pts) with iNHL based on data from a phase 3 trial (DUO) in CLL/SLL that demonstrated no negative impacts of (unscheduled) dose interruptions on response (Flinn I et al. J Clin Oncol. 2019;37(15):7523). Methods: In TEMPO, patients were randomized to receive duvelisib 25 mg BID for one 10-week cycle followed by 25 mg BID on Weeks 3 and 4 of each subsequent 4-week cycle (Arm 1) or duvelisib 25 mg BID on Weeks 1, 2, 5, 6, 9, and 10 of one 10-week cycle, and then on Weeks 3 and 4 of each subsequent 4-week cycle (Arm 2). Pts continued treatment until progressive disease (PD), unacceptable toxicity, or study withdrawal. ORR by investigator assessment, based on 2007 revised International Working Group (IWG) criteria was the primary endpoint. Results: As of data cutoff on 5 May 2021, 65 treated pts had at least 4 months of follow-up on or after study drug treatment. Across both arms, the median age was 63 years (range 34-85), and 47 (72.3%) of patients remained on duvelisib at the time of this analysis (see Table). The patient population was heavily pretreated (total prior lines: 36.9% = 1; 26.2% = 2; 10.8% = 3; and 26.2% ≥ 4); 93.8% of pts received prior rituximab and 43.1% prior bendamustine. As of data cutoff, 27.7% of pts have discontinued duvelisib, 19.7% due to PD (21.2% in Arm 1; 18.8% in Arm 2). Four patients, all in Arm 1, had a TEAE that led to treatment discontinuation. Across both arms, the ORR was 60% (39 of 65 pts), and the complete response (CR) rate was 12.3% (8 of 65 pts). Results were similar in pts who received prior rituximab (59.0%) and those who received prior bendamustine (57.1%) and were relatively consistent regardless of the number of prior treatments received (62.5%, 64.7%, 54.2% for pts with 1, 2, or ≥ 3 prior lines of therapy, respectively). Overall, the incidence of TEAEs was higher in Arm 1 vs Arm 2, including grade ≥ 3 AEs (ALT elevation 30.3% vs 3.1%; AST elevation 27.3% vs 3.1%; GI disorders 9.1% vs 0; infections 9.1% vs 3.1%; rash 6.1% vs 3.1%; and drug reaction with eosinophilia 3.0% vs 0); the incidence of grade ≥ 3 neutropenia was higher in Arm 2 (9.1% vs 18.8%). TEAEs leading to discontinuation of study drug occurred only in Arm 1 (15.2%; 5 of 33 pts) and included ALT/AST elevations (2 of 33 pts; 6.1%), skin and subcutaneous tissue disorders (2 of 33 pts; 6.1%), and pneumonia (1 of 33 pts; 3.0%). There was 1 death on study in Arm 1 due to disease progression. No TEAE-related deaths occurred in either arm. Image:Summary/Conclusion: Based on this interim analysis, continuous followed by intermittent dosing (Arm 1) and intermittent dosing (Arm 2) are both safe and effective in patients with iNHL. Efficacy was seen irrespective of prior lines of therapy, including those heavily pretreated and/or treated with prior rituximab or bendamustine. The ORR and CR are consistent with those seen in DYNAMO. Because these are early data, the differences between arms in certain types of AEs or discontinuations due to AEs are difficult to interpret. The study confirms the overall therapeutic profile of duvelisib and demonstrates that intermittent dosing may decrease the incidence of AEs without compromising efficacy.